Mounier Roman, Le Guen Ronan, Woerther Paul-Louis, Nacher Mathieu, Bonnefon Clément, Mongardon Nicolas, Langeron Olivier, Levesque Eric, Couffin Séverine, Houcke Stéphanie, Wolff Michel, Roujansky Ariane, Schimpf Caroline, Mekontso Dessap Armand, Cook Fabrice, Razazi Keyvan, Kallel Hatem
Département de Neuro-Anesthésie-Réanimation, GHU-Paris, Université de Paris, 1, Rue Cabanis, 75014, Paris, France.
Université de Paris, Paris, France.
Ann Intensive Care. 2022 Nov 17;12(1):107. doi: 10.1186/s13613-022-01079-5.
β-lactams are the main antibiotics used against wild-type AmpC-producing Enterobacterales (wtAE). However, they may fail or select AmpC-overproducing mutants. Our aim was to assess factors associated with clinical failure of β-lactams in the treatment of wtAE infection.
From September 2017 to December 2020, we prospectively included all consecutive patients treated by definitive β-lactams therapy for wtAE infection in four university ICUs. Clinical failure was defined as inadequate response to antimicrobial therapy leading to death or to the switch for a broader-spectrum antibiotic.
177 patients were included and 29.4% progressed to clinical failure. E. cloacae was the most prevalent species (42.4%) and ventilator-associated pneumonia (VAP) was the most frequent wtAE infection (69.5%). Cefepime and cefotaxime were used as definitive antibiotic treatment in 42.9% and 27.7% of patients, respectively. Occurrence of AmpC-overproduction was documented in 5.6% of patients and was associated with clinical failure (p = 0.004). In multivariate analysis, VAP (p < 0.001, OR 11.58 [95% CI 3.11-43.02] and K. aerogenes (p = 0.030, OR 3.76 [95% CI 1.13-12.46]) were independently associated with clinical failure. Conversely, cefotaxime as definitive treatment was found inversely associated with the risk of clinical failure (p = 0.022, OR 0.25 [95% CI 0.08-0.82]). After inverse probability weighting, cefotaxime showed a 20% risk reduction of clinical failure (95% CI 5-35%, p = 0.007) whatever the location of infection, the SOFA score on the day of wtAE infection, or the bacterial species.
Clinical failure in the treatment of wtAE infections is associated with the infection site and the causal microorganism. Additionally, cefotaxime use is probably protective against clinical failure in wtAE infection.
β-内酰胺类药物是用于治疗产野生型AmpC酶肠杆菌科细菌（wtAE）感染的主要抗生素。然而，它们可能治疗失败或导致产生AmpC酶过量表达的突变体。我们的目的是评估与β-内酰胺类药物治疗wtAE感染临床失败相关的因素。
2017年9月至2020年12月，我们前瞻性纳入了四所大学重症监护病房中所有接受β-内酰胺类药物确定性治疗的连续wtAE感染患者。临床失败定义为对抗菌治疗反应不足导致死亡或改用更广谱抗生素。
共纳入177例患者，29.4%进展为临床失败。阴沟肠杆菌是最常见的菌种（42.4%），呼吸机相关性肺炎（VAP）是最常见的wtAE感染类型（69.5%）。分别有42.9%和27.7%的患者使用头孢吡肟和头孢噻肟作为确定性抗生素治疗。5.6%的患者记录到AmpC酶过量表达，且与临床失败相关（p = 0.004）。多因素分析显示，VAP（p < 0.001，比值比11.58 [95%置信区间3.11 - 43.02]）和产气克雷伯菌（p = 0.030，比值比3.76 [95%置信区间1.13 - 12.46]）与临床失败独立相关。相反，发现使用头孢噻肟作为确定性治疗与临床失败风险呈负相关（p = 0.022，比值比0.25 [95%置信区间0.08 - 0.82]）。经过逆概率加权后，无论感染部位、wtAE感染当天的序贯器官衰竭评估（SOFA）评分或细菌种类如何，头孢噻肟均显示临床失败风险降低20%（95%置信区间5 - 35%，p = 0.007）。
wtAE感染的临床失败与感染部位和致病微生物有关。此外，使用头孢噻肟可能对wtAE感染的临床失败具有保护作用。
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